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The Potential Impact of Up-Front Drug Sensitivity Testing on India's Epidemic of Multi-Drug Resistant Tuberculosis.

ABSTRACT: In India as elsewhere, multi-drug resistance (MDR) poses a serious challenge in the control of tuberculosis (TB). The End TB strategy, recently approved by the world health assembly, aims to reduce TB deaths by 95% and new cases by 90% between 2015 and 2035. A key pillar of this approach is early diagnosis of tuberculosis, including use of higher-sensitivity diagnostic testing and universal rapid drug susceptibility testing (DST). Despite limitations of current laboratory assays, universal access to rapid DST could become more feasible with the advent of new and emerging technologies. Here we use a mathematical model of TB transmission, calibrated to the TB epidemic in India, to explore the potential impact of a major national scale-up of rapid DST. To inform key parameters in a clinical setting, we take GeneXpert as an example of a technology that could enable such scale-up. We draw from a recent multi-centric demonstration study conducted in India that involved upfront Xpert MTB/RIF testing of all TB suspects.We find that widespread, public-sector deployment of high-sensitivity diagnostic testing and universal DST appropriately linked with treatment could substantially impact MDR-TB in India. Achieving 75% access over 3 years amongst all cases being diagnosed for TB in the public sector alone could avert over 180,000 cases of MDR-TB (95% CI 44187 - 317077 cases) between 2015 and 2025. Sufficiently wide deployment of Xpert could, moreover, turn an increasing MDR epidemic into a diminishing one. Synergistic effects were observed with assumptions of simultaneously improving MDR-TB treatment outcomes. Our results illustrate the potential impact of new and emerging technologies that enable widespread, timely DST, and the important effect that universal rapid DST in the public sector can have on the MDR-TB epidemic in India.

SUBMITTER: Sachdeva KS

PROVIDER: S-EPMC4488842 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The Potential Impact of Up-Front Drug Sensitivity Testing on India's Epidemic of Multi-Drug Resistant Tuberculosis.

Sachdeva Kuldeep Singh KS Raizada Neeraj N Gupta Radhey Shyam RS Nair Sreenivas Achuthan SA Denkinger Claudia C Paramasivan Chinnambedu Nainarappan CN Kulsange Shubhangi S Thakur Rahul R Dewan Puneet P Boehme Catharina C Arinaminpathy Nimalan N

PloS one 20150701 7

<h4>Background</h4>In India as elsewhere, multi-drug resistance (MDR) poses a serious challenge in the control of tuberculosis (TB). The End TB strategy, recently approved by the world health assembly, aims to reduce TB deaths by 95% and new cases by 90% between 2015 and 2035. A key pillar of this approach is early diagnosis of tuberculosis, including use of higher-sensitivity diagnostic testing and universal rapid drug susceptibility testing (DST). Despite limitations of current laboratory assa ...[more]

PMID: 26132584

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Project description:BackgroundMulti-drug resistant tuberculosis (MDR TB) is a major health challenge in India that is gaining increasing public attention, but the implications of India's evolving MDR TB epidemic are poorly understood. As India's MDR TB epidemic is transitioning from a treatment-generated to transmission-generated epidemic, we sought to evaluate the potential effectiveness of the following two disease control strategies on reducing the prevalence of MDR TB: a) improving treatment of non-MDR TB; b) shortening the infectious period between the activation of MDR TB and initiation of effective MDR treatment.Methods and findingsWe developed a dynamic transmission microsimulation model of TB in India. The model followed individuals by age, sex, TB status, drug resistance status, and treatment status and was calibrated to Indian demographic and epidemiologic TB time trends. The main effectiveness measure was reduction in the average prevalence reduction of MDR TB over the ten years after control strategy implementation. We find that improving non-MDR cure rates to avoid generating new MDR cases will provide substantial non-MDR TB benefits but will become less effective in reducing MDR TB prevalence over time because more cases will occur from direct transmission--by 2015, the model estimates 42% of new MDR cases are transmission-generated and this proportion continues to rise over time, assuming equal transmissibility of MDR and drug-susceptible TB. Strategies that disrupt MDR transmission by shortening the time between MDR activation and treatment are projected to provide greater reductions in MDR prevalence compared with improving non-MDR treatment quality: implementing MDR diagnostic improvements in 2017 is expected to reduce MDR prevalence by 39%, compared with 11% reduction from improving non-MDR treatment quality.ConclusionsAs transmission-generated MDR TB becomes a larger driver of the MDR TB epidemic in India, rapid and accurate MDR TB diagnosis and treatment will become increasingly effective in reducing MDR TB cases compared to non-MDR TB treatment improvements.

Dataset Information

The Potential Impact of Up-Front Drug Sensitivity Testing on India's Epidemic of Multi-Drug Resistant Tuberculosis.

Publications

The Potential Impact of Up-Front Drug Sensitivity Testing on India's Epidemic of Multi-Drug Resistant Tuberculosis.

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